NFκB transcription factor (p65) immunohistochemistry in leprosy dermal microvasculature.

Leprosy caused by Mycobacterium leprae is characterized by a spectrum of clinical manifestations that are determined by the predominant immunological profile of the host. The recruitment of leukocytes to the sites of injury can influence the development of these profiles. Cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E participate in this process and their expression is regulated by transcriptions factors such as NFκB. To correlate the expression of cell adhesion molecules and NFκB (p65) in leprosy lesions, 30 skin biopsies of patients with leprosy [16 with the tuberculoid (TT) or borderline tuberculoid (BT) forms and 14 with the lepromatous (LL) or borderline lepromatous (BL) forms] were analyzed by immunohistochemistry. A larger mean number of cells expressing VCAM-1 (BT/TT: 18.28 ± 1.4; BL/LL: 10.67 ± 1.2; p = 0.0002), ICAM-1 (BT/TT: 9.92 ± 1.1; BL/LL: 5.87 ± 1.0; p = 0.0084) and CD62E (BT/TT: 13.0 ± 1.5; BL/LL: 2.58 ± 0.3; p = 0.0001) were observed in BT and TT lesions. The mean number of cells expressing NFκB was similar in the two clinical forms (BT/TT: 2.21 ± 2.7; BL/LL: 2.35 ± 3.1;p = 0.9285). No significant correlation was observed between expression of the transcription factor and adhesion molecules analyzed. The synthesis of ICAM-1, VCAM-1 and CD62E depends on the activation of NFκB, which acts synergistically with other transcription factors. Adequate activation of intracellular signaling pathways results in the production of endothelial adhesion molecules, contributing to the recruitment of cells to the site of injury and thus eliciting an effective inflammatory response in the elimination of the bacillus.

Relationship between growth factors and its implication in the pathogenesis of leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae which affects the skin and peripheral nervous system. The immune response of the host determines the clinical course of the disease. The tuberculoid form is the result of high cell-mediated immunity characterized by a Th1 response, whereas the lepromatous form is characterized by low cell-mediated immunity and a Th2 humoral response. The neural damage established produces marked changes in the expression of growth factors such as nerve growth factor (NGF) and its receptors (NGF-R). The expression of NGF, associated with the expression of Th1 and Th2 cytokines, might be involved in the tissue damage caused by the bacillus. Therefore, the objective of this study was to correlate the immunoexpression patterns of NGF and NGF-R in the different clinical forms of leprosy, and to associate the findings with the in situ expression of TGF-ß and clinical classification of the disease. TGF-ß, NGF and NGF-R immunoexpression was analyzed by immunohistochemistry in paraffin-embedded material. Most patients were males with a mean age of 40.7 years. TGF-ß levels were significantly higher in the lepromatous forms. No significant difference in the immunoexpression of NGF or NGF-R was observed between the clinical forms, but expression tended to be higher at the lepromatous pole. There was a significant positive correlation between NGF and NGF-R in the different clinical forms of leprosy. A significant positive correlation was observed between NGF, NGF-R and TGF-ß. It can be concluded that, even existing evidence on the role of these molecules in the clinical spectrum of leprosy.

Comparative Analysis of Human Hepatic Lesions in Dengue, Yellow Fever, and Chikungunya: Revisiting Histopathological Changes in the Light of Modern Knowledge of Cell Pathology.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Nerve Growth Factor and Pathogenesis of Leprosy: Review and Update.

Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of Mycobacterium leprae infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system.

Percepção dos estudantes de Medicina sobre as habilidades de autogestão adquiridas durante a vigência do ensino remoto / Medical students' perception about the self-management skills acquired during remote learning

Resumo: Introdução: A pandemia da Covid-19 trouxe diversos desafios para as instituições de ensino superior (IES) de todos os países. Nesse contexto, destacou-se a necessidade de reestruturação do processo de ensino-aprendizagem de forma a garantir a aquisição real de conhecimentos, bem como o desenvolvimento de métodos de estudo para que os discentes conseguissem conviver com o ensino remoto emergencial (ERE) e seus contratempos. Objetivo: Este estudo teve como objetivo investigar como ocorreu o estudo dirigido e a percepção dos discentes quanto aos ganhos de habilidades de autogestão durante o ERE. Método: Trata-se de um estudo transversal quantitativo e qualitativo, realizado com 93 estudantes de Medicina de diferentes IES brasileiras. Utilizou-se questionário semiestruturado para a coleta dos dados. Os dados foram processados no software Iramuteq, e utilizaram-se análise de similitude e nuvem de palavras, além de estatística descritiva. Resultado: Em relação ao tempo dedicado ao estudo dirigido, 59,1% dos estudantes relataram que o estabeleceram, e 57,0% afirmaram que traçaram estratégias para melhor geri-lo; 68,8% mencionaram que perceberam diferenças ao compararem os métodos de fixação de conteúdo utilizados antes e durante no ERE, e, desses, 70,3% consideraram que essas novas técnicas foram eficientes. Na análise qualitativa, analisaram-se seis corpora monotemáticos, relacionados à opinião sobre o que auxiliou e o que prejudicou a gestão das emoções e do tempo, quais estratégias de fixação de conteúdo foram utilizadas e quais habilidades de autogestão foram desenvolvidas no período do ERE. Conclusão: Evidenciou-se que, apesar das dificuldades encontradas, elas foram superadas com a adoção de estratégias centradas no desenvolvimento de habilidades de autogestão de tempo, emoções e fixação de conteúdo por parte dos estudantes, e, dessa forma, pode-se inferir que eles perceberam o desenvolvimento de algumas das habilidades essenciais para superar os novos e recentes desafios impostos pelas mudanças no planeta, como organização pessoal, dos estudos e do tempo, além das relacionadas às emoções e ao gerenciamento de recursos tecnológicos.

Abstract: Introduction: The Covid-19 pandemic presented several challenges to Higher Education Institutions (HEIs) in all countries. In this context, there is a prominent need to restructure the teaching-learning process in order to guarantee genuine knowledge acquisition, as well as the development of study methods to enable students to deal with the emergency remote teaching (ERT) and its setbacks. Objective: To investigate directed study was implemented and how students viewed the gains in self-management skills during ERT. Method: Quantitative and qualitative cross-sectional study, conducted with 93 medical students from different Brazilian HEIs. A semi-structured questionnaire was used for data collection. The data were processed using the IRAMUTEQ software, similarity analysis and word cloud, in addition to the use of descriptive statistics. Results: In relation to the time dedicated to directed study, 59.1% of the students reported having established it and 57.0% said they had outlined strategies to better manage this time; 68.8% reported having perceived differences when comparing the learning consolidation methods used before and during ERT and, of these, 70.3% considered that these new techniques were efficient. In the qualitative analysis, six monothematic corpora were analysed, relating to opinions on what helped and what hindered emotional and time management, which learning consolidation strategies were used and which self-management skills were developed during ERT. Conclusion: It was demonstrated that the difficulties encountered were overcome through the adoption of strategies to help students develop self-management skills in relation to time, emotions and learning consolidation. It can therefore be inferred that students successfully mastered some of the essential skills to overcome new and recent challenges imposed by changes in the world, such as their personal organization, studies and time, in addition to those related to emotions and management of technological resources.

In situ expression of M2 macrophage subpopulation in leprosy skin lesions.

The clinical manifestations of the leprosy depend on host immune response and the macrophages are the primary cells involved in this process. M1 and M2 cells exhibited distinct morphology, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophages express receptors such as CD163, CD68, CD206, and costimulatory molecules such as CD80 and CD86, and cytokines that trigger a suppressive or inflammatory response. Thirty-three untreated patients were selected, 17 patients had the tuberculoid leprosy (TT) and 16 had the lepromatous leprosy (LL). We performed immunohistochemistry to detect IL-13, IL-10, TGF-ß, FGF-ß, CD163, CD68, arginase 1. M2 macrophages showed significant differences between the groups studied with increase in the expression of costimulatory molecules (CD68 and CD163), arginase 1 and cytokines (IL-10, IL-13, TGF-ß and FGF-b) in the LL form. Response of M2 macrophages emerge as an alternative for a better understanding of the innate immunity in the polar forms of leprosy, highlighting the role of cytokines, arginase 1 and costimulatory molecules in the repair and suppressive responses in the lepromatous form of the disease.

E-selectin and P-selectin expression in endothelium of leprosy skin lesions.

Leprosy is an infectious-contagious disease whose clinical evolution depends on the immune response pattern of the host. Adhesion molecules and leukocyte migration from blood to tissue are of the utmost importance for the recognition and elimination of infectious pathogens. Selectins are transmembrane glycoproteins that share a similar structural organization and can be divided into three types according to their site of expression. The biopsies were cut into 5µm thick sections and submitted to immunohistochemistry using antibodies against E-selectin and P-selectin. The number of E-selectin-positive cells was significantly higher in the tuberculoid form than in the lepromatous form. The immunostaining pattern of P-selectin differed from that of E-selectin. Analysis showed a larger number of endothelial cells expressing CD62P in the lepromatous form compared to the tuberculoid form. The presence of these adhesins in the endothelium contributing to or impairing the recruitment of immune cells to inflamed tissue and consequently influences the pattern of immune response and the clinical presentation of the disease.

Seroepidemiology of arbovirus in communities living under the influence of the lake of a hydroelectric dam in Brazil / Soroepidemiologia das arboviroses em comunidades que vivem sob a influência do lago de uma usina hidrelétrica no Brasil

Abstract Introduction The arbovirus proposes an important problem of public health in Brazil, especially in the Amazon, due to its capacity to cause outbreaks with high levels of morbidity-mortality in humans as well as in animals. Objective This paper had the objective to estimate the prevalence of antibodies to arbovirus in communities that live under the influence of the artificial lake of UHE Tucuruí in the State of Pará, Brazil. Method The analytical transversal study has selected 657 blood serum samples of individuals over 18, both genders, residents at the Sustainable Development Reserves (SDR) in the region of the lake of UHE Tucuruí. The epidemiological information has been registered in an instrument especially designed for such a study and the blood samples were collected in two periods of high and low tide of the lake. The blood serum tests were performed by the method of hemagglutination inhibition (HI). Results The results revealed a prevalence of positive antibodies to arbovirus of 85.0%, being 84.1% related to Flavivirus (vaccine strain of YFV), 25.5% related to Alphavirus and 34.6% to Bunyavirus. The results of serum prevalence to arbovirus between the periods of high tide and low tide have revealed significance amongst the Alphavirus, not observed in the other families. Conclusion In general, the data from this paper have suggested that the anthropoid actions on the environment of the lake have become determinant factors for the prevalence of arboviral antibodies.

Resumo Introdução Os arbovírus representam um importante problema de saúde pública no Brasil, especialmente na Amazônia, devido à sua capacidade de causar surtos em seres humanos e em animais. Objetivo Este trabalho teve o objetivo de estimar a prevalência de anticorpos para arbovírus em comunidades que vivem sob a influência do lago artificial de barragem hidrelétrica no Brasil. Método O estudo transversal analítico selecionou 657 amostras de sangue de indivíduos de ambos os sexos, residentes na região do lago. As informações epidemiológicas foram registradas em um instrumento concebido para este estudo e as amostras de sangue foram coletadas em períodos de maré alta e maré baixa do lago. Os testes sorológicos foram realizados pelo método de inibição da hemaglutinação (IH). Resultados Os resultados revelaram uma prevalência de anticorpos positivos para arbovírus de 85%, com 84,1% referentes ao Flavivirus (cepa vacinal de FA), 25,5% em relação ao Alphavirus e 34,6% para Orthobunyavirus. Os resultados de prevalência de anticorpos para arbovírus entre os períodos de maré alta e maré baixa revelaram significância entre os Alphavirus. Conclusão Em geral, os dados sugerem que as ações antrópicas no ambiente do lago tornaram-se fatores determinantes para a prevalência de anticorpos arbovirais.